The construction and evaluation of heart preservation model for jumping donor heart based on extracorporeal membrane oxygenation technology_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YIN Shijie ¹ , YUE Xiao ¹ , WANG Chunhua ¹ , WU Wei ² , QIN Guanbin ² , LUO Lan ² , HUANG Qiangxin ³ ,  HE Guixin ⁴

1. Guangxi University of Chinese Medicine, Nanning, 530200, P. R. China;
2. Department of Anesthesiology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, P. R. China;
3. Department of Thoracic and Cardiac Surgery, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, P. R. China;
4. Department of the Second Ward of Cardiovascular Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, P. R. China;

Corresponding?author：

HE Guixin, Email: he_guixin@163.com

Keywords：

In vitro beating pig heart; animal model; extracorporeal membrane oxygenation; myocardial protection

DOI：

10.7507/1007-4848.202404066

Video：

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Objective To explore the construction of heart preservation model of empty beating donor based on extracorporeal membrane oxygenation (ECMO). Methods From January 2022 to August 2023, 20 Guangxi Bama miniature pigs weighing 25-30 kg were selected, half male and half female. Under general anesthesia and heparinization, a midline thoracotomy was performed. The pericardium was cut after freeing the anterior and posterior vena cavae, and a perfusion needle was inserted near the brachiocephalic artery in the ascending aorta, connected to a blood collection bag to collect 500-600 mL of blood. The anterior and posterior vena cavae were ligated, the aorta was blocked and perfused with HTK solution to stop the heart beating. The superior and inferior vena cavae were cut off, the right pulmonary vein was decompressed, the aorta and left and right pulmonary arteries and veins were cut off, and the whole heart was removed. An ECMO device was used to continuously perfuse a cardioprotective solution mainly composed of oxygenated warm blood, maintaining the isolated pig heart beating for 8 hours, monitoring (once/hour) ECMO perfusion parameters, blood gas indicators, perfusate electrolytes, detecting inflammatory factors, myocardial enzymes, myoglobin, and troponin levels. Myocardial tissue was taken for hematoxylin-eosin (HE) staining to observe myocardial cell damage and evaluate the quality of heart preservation. Results Among the 20 isolated beating preservation pig hearts, 17 successfully resumed beating, 3 experienced ventricular fibrillation, resuscitated after intracardiac electrical defibrillation, and all 20 pig hearts successfully beat for 8 hours. There was no statistical difference in ECMO perfusion parameters, blood gas indicators, perfusate electrolytes, and inflammatory factors at each time point (P>0.05). There were statistical increases in myocardial enzymes, myoglobin, and troponin levels (P<0.05). HE staining results suggested that there was no severe myocardial damage. Conclusion ECMO technology can be used for pig heart preservation with good results, and this study provides experimental evidence for improving heart preservation research in clinical heart transplantation.

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12.	Hu CX, Chen WH, He JX, et al. Lung transplantation in China between 2015 and 2018. Chin Med J (Engl), 2019, 132(23): 2783-2789.
13.	Chocron S, Kaili D, Yan Y, et al. Intermediate lukewarm (20 degrees c) antegrade intermittent blood cardioplegia compared with cold and warm blood cardioplegia. J Thorac Cardiovasc Surg, 2000, 119(3): 610-616.
14.	Buckberg GD. Oxygenated cardioplegia: Blood is a many splendored thing. Ann Thorac Surg, 1990, 50(2): 175-177.
15.	Minatoya K, Okabayashi H, Shimada I, et al. Intermittent antegrade warm blood cardioplegia for CABG: Extended interval of cardioplegia. Ann Thorac Surg, 2000, 69(1): 74-76.
16.	馬嘯龍, 陳博, 劉成, 等. 體外膜肺氧合中血栓炎癥反應及管路生物相容性的研究進展. 臨床檢驗雜志, 2023, 41(6): 444-448.Ma XL, Chen B, Liu C, et al. Progress in the study of thrombo-inflammatory response and pipeline biocompatibility in extracorporeal membrane oxygenation. Chin J Clin Lab Sci, 2023, 41(6): 444-448.
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18.	Miles JA, Quispe R, Mehlman Y, et al. Racial differences and mortality risk in patients with heart failure and hyponatremia. PLoS One, 2019, 14(6): e0218504.
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20.	向采霏, 姜文凱, 郎澤昆, 等. 心臟體外循環術后高鈉血癥的原因探討. 心血管病學進展, 2021, 42(12): 1089-1092.Xiang CF, Jiang WK, Lang ZK, et al. The cause of hypernatremia after cardiopulmonary bypass. Adv Cardiovasc Dis, 2021, 42(12): 1089-1092.
21.	Ying WZ, Aaron K, Wang PX, et al. Potassium inhibits dietary salt-induced transforming growth factor-beta production. Hypertension, 2009, 54(5): 1159-1163.
22.	Lorenz JN, Loreaux EL, Dostanic-Larson I, et al. ACTH-induced hypertension is dependent on the ouabain-binding site of the alpha2-Na⁺-K⁺-ATPase subunit. Am J Physiol Heart Circ Physiol, 2008, 295(1): H273-H280.
23.	Hunter RW, Bailey MA. Hyperkalemia: Pathophysiology, risk factors and consequences. Nephrol Dial Transplant, 2019, 34(Suppl 3): iii2-iii11.
24.	Válek M, Roblová L, Ra?ka I, et al. Hypocalcaemic cardiomyopathy: A description of two cases and a literature review. ESC Heart Fail, 2020, 7(3): 1291-1301.
25.	Chrysant SG. Proton pump inhibitor-induced hypomagnesemia complicated with serious cardiac arrhythmias. Expert Rev Cardiovasc Ther, 2019, 17(5): 345-351.
26.	侯安存. 兒童心肌損傷檢測指標的研究進展及優選劣汰. 臨床和實驗醫學雜志, 2015, 14(20): 1750-1753.Hou AC. Research progress and optimal selection of indicators for cardiac myocardial injury detection in children. J Clin Exp Med, 2015, 14(20): 1750-1753.
27.	盧美娜, 華春珍, 賈艷會. 病毒性心肌炎患兒外周血心肌酶譜指標變化及與預后的關系. 中國婦幼保健, 2022, 37(6): 1018-1021.Lu MN, Hua CZ, Jia YH. Changes in peripheral blood cardiomyocyte enzyme spectrum indicators in children with viral myocarditis and their relationship with prognosis. Matern Child Health Care China, 2022, 37(6): 1018-1021.
28.	肖文, 胡長新, 周士娣. 有機磷中毒早期心肌損傷患者血清NT-proBNP、IL-18、α-HBDH水平變化及臨床意義. 牡丹江醫學院學報, 2024, 45(1): 47-50, 63.Xiao W, Hu CX, Zhou SD. Changes in serum NT-proBNP, IL-18, and α-HBDH levels and clinical significance in patients with early myocardial injury due to organic phosphorus poisoning. J Mudanjiang Med Univ, 2024, 45(1): 47-50, 63.

1. Lee HY, Oh BH. Heart transplantation in Asia. Circ J, 2017, 81(5): 617-621.
2. Hess NR, Ziegler LA, Kaczorowski DJ. Heart donation and preservation: Historical perspectives, current technologies, and future directions. J Clin Med, 2022, 11(19): 5762.
3. Qin G, Su Y, Sj?berg T, et al. Oxygen consumption of the aerobically-perfused cardioplegic donor heart at different temperatures. Ann Transplant, 2018, 23: 268-273.
4. 李建輝, 徐驍, 謝海洋, 等. 中國移植器官保護專家共識 (2022版). 器官移植, 2022, 13(2): 144-160.Li JH, Xu X, Xie HY, et al. Chinese expert consensus on organ protection of transplantation (2022 edition). Organ Transpl, 2022, 13(2): 144-160.
5. Van Caenegem O, Beauloye C, Bertrand L, et al. Hypothermic continuous machine perfusion enables preservation of energy charge and functional recovery of heart grafts in an ex vivo model of donation following circulatory death. Eur J Cardiothorac Surg, 2016, 49(5): 1348-1353.
6. Ragalie WS, Ardehali A. Current status of normothermic ex-vivo perfusion of cardiac allografts. Curr Opin Organ Transplant, 2020, 25(3): 237-240.
7. 李勇男. 不同心臟保存液對供體心臟保護效果評價與供體心臟中冷誘導RNA結合蛋白作用機制的研究. 蘭州大學, 2019.Li YN. Compared efficacy of preservation solutions on the outcome of heart transplantation and effects of cold-inducible RNA-binding protein in the cold stored hearts. Lanzhou University, 2019.
8. Lund LH, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirtieth Official Adult Heart Transplant Report-2013; Focus theme: Age. J Heart Lung Transplant, 2013, 32(10): 951-964.
9. 孫永豐, 董念國, 劉金平, 等. 供心冷缺血時間對臨床心臟移植近中期療效的影響分析. 中華器官移植雜志, 2014, 35(6): 329-332.Sun YF, Dong NG, Liu JP, et al. Effect of ischemic time on survival after heart transplantation. Chin J Organ Transplant, 2014, 35(6): 329-332.
10. Wyss RK, Méndez-Carmona N, Sanz MN, et al. Mitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death-consequences of ischemic duration. J Heart Lung Transplant, 2019, 38(6): 647-657.
11. Ribeiro R, Ghashghai A, Yu F, et al, Comparison between Steen and Somah solutions as primary perfusate components for ex vivo heart perfusion. Canadian J Cardiol, 2017, 33(10): S69.
12. Hu CX, Chen WH, He JX, et al. Lung transplantation in China between 2015 and 2018. Chin Med J (Engl), 2019, 132(23): 2783-2789.
13. Chocron S, Kaili D, Yan Y, et al. Intermediate lukewarm (20 degrees c) antegrade intermittent blood cardioplegia compared with cold and warm blood cardioplegia. J Thorac Cardiovasc Surg, 2000, 119(3): 610-616.
14. Buckberg GD. Oxygenated cardioplegia: Blood is a many splendored thing. Ann Thorac Surg, 1990, 50(2): 175-177.
15. Minatoya K, Okabayashi H, Shimada I, et al. Intermittent antegrade warm blood cardioplegia for CABG: Extended interval of cardioplegia. Ann Thorac Surg, 2000, 69(1): 74-76.
16. 馬嘯龍, 陳博, 劉成, 等. 體外膜肺氧合中血栓炎癥反應及管路生物相容性的研究進展. 臨床檢驗雜志, 2023, 41(6): 444-448.Ma XL, Chen B, Liu C, et al. Progress in the study of thrombo-inflammatory response and pipeline biocompatibility in extracorporeal membrane oxygenation. Chin J Clin Lab Sci, 2023, 41(6): 444-448.
17. 周玉陽. 低溫含血Plegisol液微流量持續灌注對熱缺血豬心的保護作用. 鄭州大學, 2011.Zhou YY. The myocardial protection effect of micro-flow perfusionwith hypothermic bloody plegisol solution on warm ischemic pig heart graft. Zhengzhou University, 2011.
18. Miles JA, Quispe R, Mehlman Y, et al. Racial differences and mortality risk in patients with heart failure and hyponatremia. PLoS One, 2019, 14(6): e0218504.
19. Kinugawa K, Sato N, Inomata T, et al. Novel risk score efficiently prevents tolvaptan-induced hypernatremic events in patients with heart failure. Circ J, 2018, 82(5): 1344-1350.
20. 向采霏, 姜文凱, 郎澤昆, 等. 心臟體外循環術后高鈉血癥的原因探討. 心血管病學進展, 2021, 42(12): 1089-1092.Xiang CF, Jiang WK, Lang ZK, et al. The cause of hypernatremia after cardiopulmonary bypass. Adv Cardiovasc Dis, 2021, 42(12): 1089-1092.
21. Ying WZ, Aaron K, Wang PX, et al. Potassium inhibits dietary salt-induced transforming growth factor-beta production. Hypertension, 2009, 54(5): 1159-1163.
22. Lorenz JN, Loreaux EL, Dostanic-Larson I, et al. ACTH-induced hypertension is dependent on the ouabain-binding site of the alpha2-Na⁺-K⁺-ATPase subunit. Am J Physiol Heart Circ Physiol, 2008, 295(1): H273-H280.
23. Hunter RW, Bailey MA. Hyperkalemia: Pathophysiology, risk factors and consequences. Nephrol Dial Transplant, 2019, 34(Suppl 3): iii2-iii11.
24. Válek M, Roblová L, Ra?ka I, et al. Hypocalcaemic cardiomyopathy: A description of two cases and a literature review. ESC Heart Fail, 2020, 7(3): 1291-1301.
25. Chrysant SG. Proton pump inhibitor-induced hypomagnesemia complicated with serious cardiac arrhythmias. Expert Rev Cardiovasc Ther, 2019, 17(5): 345-351.
26. 侯安存. 兒童心肌損傷檢測指標的研究進展及優選劣汰. 臨床和實驗醫學雜志, 2015, 14(20): 1750-1753.Hou AC. Research progress and optimal selection of indicators for cardiac myocardial injury detection in children. J Clin Exp Med, 2015, 14(20): 1750-1753.
27. 盧美娜, 華春珍, 賈艷會. 病毒性心肌炎患兒外周血心肌酶譜指標變化及與預后的關系. 中國婦幼保健, 2022, 37(6): 1018-1021.Lu MN, Hua CZ, Jia YH. Changes in peripheral blood cardiomyocyte enzyme spectrum indicators in children with viral myocarditis and their relationship with prognosis. Matern Child Health Care China, 2022, 37(6): 1018-1021.
28. 肖文, 胡長新, 周士娣. 有機磷中毒早期心肌損傷患者血清NT-proBNP、IL-18、α-HBDH水平變化及臨床意義. 牡丹江醫學院學報, 2024, 45(1): 47-50, 63.Xiao W, Hu CX, Zhou SD. Changes in serum NT-proBNP, IL-18, and α-HBDH levels and clinical significance in patients with early myocardial injury due to organic phosphorus poisoning. J Mudanjiang Med Univ, 2024, 45(1): 47-50, 63.

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Latest ArticlesThe construction and evaluation of heart preservation model for jumping donor heart based on extracorporeal membrane oxygenation technology

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